These PhD. topics are available for study in 2017/2018 in our department:

Biodegradable polymeric prodrugs for targeted inhibition of the metastatic process

Annotation

Metastatic process is usually a live-limitting factor during the treatmnent of various neoplastic deseases. The major aim of this project is to design, synthesize and study the physico-chemical and biological properties of the biodegradable polymer prodrugs of anticancer drugs and inhibitors of matrix metaloproteasis. Specificity of action will be obtained by their targeting with molecules significantly binding to VEGF or AT1R receptors on the neovasculature of metastases. We suppose that treatment with proposed polymer conjugates will enable simultaneously target several steps involved in the tumor progression and metastatic spread.Polymer drug carriers will be characterized by various physico-chemical methods. Their biological activity will be evaluated in vitro on cell cultures by the student themselves. Further biological evaluation of prepared samples will be solved in cooperation with our local and foreign partner biologicists. The student will broaden their knowledge in the field of novel drug delivery and they will learn new skills of modern polymerization techniques and synthetic and instumental methods.

Synthesis and study of properties of well-defined high molecular weight polymer nanogels or star-like polymers serving as drug carriers for anti-cancer drugs and inhibitors of anti-apoptotic proteins is the aim of this project. These drug carriers will be synthetized by controlled solution or emulsion radical polymerization technique. The polymer carriers will be designed as biodegradable structures, which undergo stimuli-sensitive degradation within peripheral tumor part to fragments enabling rapide extravasation into the tumor and drug release. Disertation will be based on the polymer synthesis par and physico-chemical characterisation of polymer material. Their biological activity will be evaluated in vitro on cell cultures by the student themselves. Further biological evaluation of prepared samples will be solved in cooperation with our local and foreign partner biologicists. The student will broaden their knowledge in the field of novel drug delivery and they will learn new skills of modern polymerization techniques and synthetic and instumental methods.

Topic

Polymer carriers for drugs with new types of linkers

Annotation

The standard low-molecular-weight drugs suffer from a number of principal drawbacks, including in particular their rapid elimination from the body, side toxicity, often poor solubility and non-specific action. However, if the given therapeutic agent is linked via an appropriate spacer to a suitable carrier the above-mentioned shortcomings can be completely eliminated. Long-time development has shown that the ideal carriers are water-soluble polymers such as poly(ethylene oxide), copolymers of N-(2-hydroxypropyl)methacrylamide (HPMA) and some others. Such polymers are completely nontoxic and biocompatible themselves, and, consequently, the active substances bound to them behave similarly. We talk about so-called polymer conjugates which can circulate in the blood several days, have significantly suppressed toxicity compared to the free drug and thanks to the possibility of passive or active targeting they can specifically act at the target site. However, the desired effect can be achieved only if the bond (linker) between polymer carrier and drug is long-term stable in blood circulation and also easily degraded in the site of action. This condition is further limited by the nature of the reactive groups useful for binding on the drug itself. As a result, only few well-functioning systems on that principle have been developed and described so far, and, in addition, for a very limited group of therapeutics. Aim of the project is the design and synthesis of polymer carriers based on HPMA copolymers with different types of reactive groups suitable for a wide range of drugs, in particular cancerostatics. The focal point will consist of organic and polymer synthesis, characterization of polymer systems using instrumental techniques and also of the work with scientific literature. Selected conjugates will be then tested by the cooperating biologists in terms of their therapeutic activity.

Topic

Polymer drug carriers for immunooncotherapy

Annotation

The aim of the project is synthesis and study of properties of polymer prodrugs enabling targeting of anticancer drug and immunomodulatory agents. The project is focused on investigation of new polymer prodrug, mainly synthesis of micellar polymer carrier, and attachment of drug and other biologically active compounds to polymer carriers. The topic is suitable for graduates of chemical or pharmaceutical faculties. We offer interesting and diverse work in young dynamic team in highly reputable academic institution.

Topic

New Generation of Targeted Polymer Cancerostatics

Annotation

Combination of synthetic and natural macromolecules may provide new sophisticated materials. Some of the polymer systems can be used for controlled drug release and targeted drug delivery. Hydrophilic synthetic polymers containing various biologically active peptides and proteins will be designed and synthesized in this project. The peptides or proteins (e.g. antibodies and antibody fragments) will be used as targeting ligands enabling enhanced accumulation of the polymer drug conjugate in the site of desired therapeutic effect. We will optimize the methods of attachment of the targeting ligands to the polymer carrier with the aim to preserve the biological activity. One possibility is to take advantage of non-covalent interaction between peptides (e.g. a coiled coil interaction). The polymer carriers will be based mostly on copolymers of N-(2-hydroxypropyl)methacrylamide or poly(ethylene glycol). The properties of the polymer systems will be thoroughly studied using various physico-chemical methods, e.g. liquid chromatography, mass spectroscopy, light scattering, circular dichroism and NMR. Biological properties will be studied in collaboration with another institutions.